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Workplace hazards during pregnancy
HONORABLE MENTION PAPER
WORKPLACE HAZARDS DURING PREGNANCY John L. Frattarelli, MD, CPT, MC,* USA, and Gregory R. Moore, CDR, MC,t USN
Currently, very little is known about potential reproductive hazards found in the workplace. Yet, every day pregnant women are exposed to toxins and physical agents that are potentially harmful to them and theirfetuses. Concerned obstetric patients frequently inquire about the possibility that agents they encounter on their jobs may have an adverse impact on their pregnancy. A variety of workplace exposures have been studied, and existing data allow us to make appropriate recommendations to working women. Unfortunately, data are limited regarding the majority of exposures. Certainly, the reproductive risks of radiation and heavy metals have been known for years. This is not the case with most other exposures. With the female workforce growing, more women are being exposed to these potential reproductive hazards. In this article, we review the recent literature to assess the hazards to the pregnant female and the fetus from workplace exposure to physical stress, radiation, lead, biologic agents, anesthetics, and solvents. In addition, we offer guidelines and resources for evaluating and managing the hazards found in the workplace. (P rim Care Update OblGyns 1998;5:54-59. 0 1998
Elsevier reserved.)
Science
Inc.
All
rights
From the Department of Obstetrics and Gynecology. *Walter Reed Army Medical Center, Washington, DC; and tNationa1 Naval Medical Center, Bethesda, Maryland. The views expressed herein are those of the authors and do not reflect the official policy or position of the Department of the Army, the Department of the Navy. the Department of Defense, or the U.S. Government.
Studying workplace reproductive hazards is a relatively new field for research and clinical medicine. Approximately two thirds of women of childbearing age have jobs outside the home. More than 1 million of these women become pregnant each year. As more women work outside of the home, they are exposed to a variety of occupational risks, including possible reproductive hazards. There is a general lack of valid data demonstrating the toxicity of potential occupational hazards in pregnancy. There is an even greater paucity of valid information and research about the adverse effects of preconceptional exposures. What is known is that there are a variety of adverse reproductive endpoints and environmental exposures, on and off the job, that may play a role in reproductive outcomes. Ten percent to 20% of all recognized pregnancies end in miscarriage between the fourth and 20th week. Additionally, 2-3% of all newborns have major congenital anomalies. Approximately 60% of these anomalies have no known cause. Some likely involve environmental or occupational factors. The pregnant woman is justifiably concerned about the potential dangers in the workplace that may affect her pregnancy. As manufacturing processes change, new technology comes on line, and women work in traditionally male fields, new reproductive hazards will emerge and known hazards may become more important. Approxi-
54
Inc.,
0 1998
Elsevier
Science
all rights
reserved.
1068-607X/98/$19.00
mately 60,000 chemicals are in common use, with an additional 600 new chemicals entering the marketplace each year. Few of these chemicals have been tested for developmental toxicity in experimental animals, and even fewer in human subjects. Our knowledge about the potential reproductive risk from even low-level exposure to a mixture of agents, which is common in the workplace, is even less certain. Toxic exposure can cause a range of effects, including germ cell alteration, menstrual irregularity, embryologic effects, and implantation abnormalities. Ovarian toxicity has been linked to ionizing radiation, chemotherapy, tobacco use, and other exposures. Although better protected by virtue of the bloodtestes barrier, the male gonads can also be harmed. Damage to sperm production, however, is often reversible because the male, unlike the female, has a renewing germ cell pool. During pregnancy, the timing of the insult is crucial to the embryologic effect. In the early preimplantation period a teratogenic insult probably creates an “all or none” effect. When the embryo consists of only a few cells, loss of one or two of these cells will result in either the death of the embryo or the remaining toti-potential cells will take over the functions of the lost cells, resulting in an intact organism. Damage during the embryologic period, which extends from implantation to day 56 of gestation, may also cause death or gross structural abnormalities. During the fetal period, day 56 of gestation until birth, dangerous exposures are most likely to produce growth and central nervous
. PI1 SlO68.607X(97)00114-5
Prim
Care
Update
ObiGyns
WORKPLACE
system (CNS) deficits, although serious teratogenic effects can occur after exposure to agents like radiation and viruses during the third trimester.
Ergonomics Many studies have shown that working women have better pregnancy outcomes than unemployed women. However, frequently confounding factors such as age, education, family size, and access to medical care are present. Working women tend to have better health insurance and other socioeconomic factors that may result in better compliance with prenatal care and counteract small occupational risks. Recent reports suggest an association with strenuous physical work, preterm delivery, and low birth weight. In a large study conducted in New York, Homer et all examined the combined outcome of preterm delivery and low birth weight in young disadvantaged white, black, and Hispanic women. After adjusting for confounding variables, they found an increased risk of low birth weight and preterm delivery in women who reported high levels of occupational physical exertion. Many physiologic changes occur during pregnancy that can affect the type and duration of work that women can safely and comfortably perform. Early in her pregnancy, a woman may experience nausea, vomiting, and dizziness. Jobs where odors or motion are present may exacerbate these normal and expected symptoms. Physiologic changes in the cardiovascular system during pregnancy produce an increase in blood volume, cardiac output, heart rate, inferior vena caval pressure, and a decrease in diastolic blood pressure. These cardiovascular alterations can be affected by temperature, humidity, and barometric pressure. Pulmonary Volume
5. Number
1. 1998
changes during pregnancy create an increased tidal volume, minute ventilation, oxygen demand, work of breathing, capillary dilation throughout the respiratory tract, and decreased residual lung volume. Smoke, asphyxiant agents, and irritant gasescan affect the pulmonary changes experienced during pregnancy. The additional work of breathing during pregnancy may make the use of personnel protective devices, such as respirators, dilficult. Likewise, the increased metabolic demands of pregnancy can hinder the woman’s ability to perform strenuous, repetitive tasks. Musculoskeletal changes cause an increase in lordosis of the lumbosacral spine and a posterior shift of the patient’s center of gravity. These changes place the pregnant worker at an increased risk for loss of balance, lower back ache, and muscle strains. She should be warned to avoid wearing high heels and lifting heavy items. The enlarging uterus makes it necessary to lift loads further from the axial skeleton, thus markedly increasing the work of lifting. The pregnant patient is also at an increased risk for repetitive motion injuries when performing tasks such as typing and playing musical instruments. An increase in maternal metabolic rate coupled with the fetal demand for heat dissipation makes the pregnant woman less tolerant to hot, humid environments and working conditions. Jobs requiring protective clothing can add to this heat burden. Furthermore, standing for long periods can decrease uteroplacental blood flow and may lead to a decrease in birth weight. In general, workloads handled easily before pregnancy are usually well tolerated during pregnancy. Simple modifications such as decreasing the work pace, foot rests to relieve lumbosacral disc pressure while sitting, and increased rest breaks are often sufficient enough to
HAZARDS
DURING
PREGNANCY
allow the woman to continue working safely. Fortunately, some physiologic adaptations may help protect the fetus from environmental exposures. The increase in blood volume may dilute the concentration of toxins reaching the maternal tissues. Likewise, increases in renal plasma flow and glomerular filtration rate allow for an increased rate of elimination of toxic metabolites. In a recent case-control study, Spinillo et al2 evaluated 160 nulliparous patients with severe preeclampsia and 320 normotensive nulliparous control subjects. They divided the patients into four groups based on their level of activity. They concluded that there was a significant linear trend relating degree of physical activity at work to the risk of preeclampsia. However, for every study supporting physical work during pregnancy as a hazard, there is also an article advocating that work and pregnancy outcome are unrelated. IONIZING RAIMATI~N Ionizing radiation is so called because it has sufficient energy to displace orbital electrons, resulting in the formation of electronically charged ions in matter. It includes x-rays, y rays, (Y particles, p particles, and neutrons. The principal unit of exposure is the roentgen, defined as the measure of the amount of ionizations produced in the air. Units of absorbed radiation include the Gray and the rad. One Gray equals 100 rad or 100 rem. Different types of radiation produce differing amounts of biologic damage. The sievert (sv) or rem (1 sv = 100 rem) adjusts for the difference in effect produced by the different types of radiation. X-rays, y rays, and /3 particles all produce equivalent damage; however, cy particles produce 20 times the damage of the others. Fortunately, (Yparticles penetrate poorly, but they are hazardous if consumed in food or water. 55
Everyone is continuously exposed to low-dose background radiation found in cosmic rays, soil, rock, air, and natural radioisotopes. Background radiation exposure increases at high altitudes because the atmosphere filters out fewer cosmic rays. This information can be pertinent to people whose occupations require frequent flying. An individual flying from New York to Tokyo at the usual altitude of 40,000 feet will receive radiation that is equivalent to approximately two chest x-rays. Workplace radiation exposures usually result from whole-body external radiation. The most significant exposures occur during accidents on the job when the radiation source is no longer contained by protective measures. Occupational sources include nuclear fuel, diagnostic x-ray, radioisotopes, and radioactive minerals. The degree of damage produced by ionizing radiation is influenced by several factors, including type, dose, dose disand target tissue tribution, sensitivity. Rapidly dividing cells of the embryo and reproductive germinal epithelium are particularly radiosensitive. The complex development of the CNS, which takes place throughout pregnancy and into postpartum life, makes it a common target for radiation damage. The gonads are highly sensitive to the effects of irradiation, with resulting temporary and permanent effects on fertility depending on the dose of radiation received.3 Permanent sterility has been reported in women and men from a single dose of 600 rads and 400 rads, respectively. Effects of prenatal exposure are highly time dependent, ranging from an all or none effect during preimplantation to teratogenic effects, especially microcephaly and eye anomalies during organogenesis. Mental retardation, growth restriction, and CNS deficits can occur with exposure later in gestation. 56
However, there seems to be a radiation threshold, in that there have been no observable fetal effects with an exposure of less than 5 rads. With the exception of a lumbosacral spine series (0.64 rem), bone scan (0.5 rem), and intravenous pyelogram (0.64 rem), there are very few diagnostic radiation studies that result in doses of more than 0.5 rem. Occupational Safety and Health Administration occupational limits for ionizing radiation to the adult gonads are 1.25 rems per calendar quarter or 5 rems per year. The National Council on Radiation Protection and Measurements suggests that occupational exposure to an embryo or fetus not exceed 0.5 rems total dose.4 Although radiation exposure is a definite threat to the pregnant patient given the proper precautions, most patients working with ionizing radiation can continue employment. When counseling patients regarding the risk of radiation exposure, the dose, frequency, and precise timing of the exposure should be estimated. Radiation safety personnel can obtain radiation badge readings and assist in determining the amount of exposure.
NONIONIZING
RADIATION
Nonionizing radiation is ubiquitous. Radiofrequency radiation comes from television, radio, radar, microwaves, computer terminals, heating blankets, toasters, and more. Nonionizing radiation damages tissues not by ionization but by cellular heating. The eye, testes, CNS, and developing embryo potentially have high sensitivities to the thermal effects of radiofrequency radiation. However, industrial and home exposure are well below the threshold to cause teratogenic effects owing to modern protective devices, such as screens in microwave ovens that are 100% effective in shielding all radiation.
Video display terminals (VDTs), which produce very low frequency and extremely low frequency radiation, are common both at work and in the home. Physicians frequently encounter questions from patients concerning the safety of these devices. The cathode ray tubes of VDTs are similar to television tubes and emit x-rays. However, this ionizing radiation is well absorbed by the glass screen and ionizing radiation emissions are negligible. Literature from the early 1980s contained several cases concerning the potential reproductive effects and increased miscarriage rates in females exposed to VDTs during pregnancy. However, most subsequent epidemiologic analyses found equivocal or no effect on pregnancies associated with VDT use. The most complete study of VDTs and pregnancy was reported in 1991 by researchers at the National Institution for Occupational Safety and Health.5 Schnorr et al used a cohort investigation involving directory assistance operators who used only VDTs and general telephone operators who used work stations without VDTs. They concluded that the use of VDTs and exposure to the accompanying electromagnetic fields were not associated with an increase in spontaneous abortions. Thus, there is no scientific evidence to suggest that women need to curtail or discontinue the use of VDTs during pregnancy. Noise is transmitted clearly through the abdomen; some frequencies are actually accentuated. There is no effective way to shield the fetus from noise. There is some evidence that in utero exposure to loud noises greater than 85 dBA can cause hearing loss. Lalande et al” evaluated 131 children whose mothers had worked at least 1 month during pregnancy in a setting where noise levels ranged from 65 to 95 dBA. A strong dose-response relationship was noted between noise level during pregnancy and Prim
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WORKPLACE subsequent hearing loss in children. Among children whose mothers were exposed to levels of 85-95 dBA during the course of their pregnancy, 24% had significant hearing loss; however, only 12.9% experienced hearing loss when exposed to noise levels less than 85 dBA. Exposure to heat and hot environments can occur in a variety of industries and occupations. In extreme situations, the precise regulation of internal body temperature can be overcome by environmental heat. Several studies have linked an increase in the core temperature during early pregnancy to neural tube defects. Shiota,7 in a study involving human abortus specimens, found a highly significant association between reported febrile illness of 39 C during pregnancy and exencephaly. Because the most common cause of an increased core temperature in the pregnant female is maternal fever, studies have tended to rely on this association. As with most studies of pregnancy outcomes, however, recall bias is a common problem. It is conceivable that in certain working conditions, such as hot, humid climates and industrial operation (mining and metal processing, laundering, construction, food preparation, textiles, canning, and manufacturing of plastics, rubber, glass, and chemicals), the maternal core temperature could rise to the critical level of 39 C. Milunsky et al8 in 1992 reported on a cohort of 23,491 women in a prospective follow-up study. They found that first-trimester maternal heat exposure in the form of hot tubs, sauna, or fever was associated with an increased risk of neural tube defects. Exposure to electric blankets was not associated with an increased risk. Therefore, women who have experienced hyperthermic episodes during early pregnancy should be counseled about the possibility of teratogenic effects Volume
5, Number
1, 1998
and offered a-fetoprotein screening and level 2 ultrasound evaluation. BIOLOGIC
AGENTS
Workers in the health care system, schools, and day care centers may be exposed to a number of potentially harmful infectious agents, including rubella, parvovirus, cytomegalovirus (CMV), varicella, hepatitis B, and human immunodeficiency virus. All workers in such areas should strictly adhere to universal precautions and infection control measures. In doing this, they will greatly decrease their risk of infection. Rubella, CMV, and varicella are teratogenic after maternal exposures well into the second trimester. Specific immunoglobulins can be used prophylactically in some circumstances after contact with infected patients and children. Although vaccines are available for rubella, varicella, hepatitis B, mumps, and measles, there are still a significant number of nonimmune individuals in the population, especially in immigrant communities. However, the live vaccines for measles, mumps, rubella, polio, and yellow fever are contraindicated in pregnancy because of the throrctical risk of transmission of the virus to the fetus. Not only is CMV ubiquitous, but it remains infectious on surfaces, and approximately half of the adult population is susceptible. The virus infects the fetus vertically. Most mothers and fetuses are asymptomatic during CMV infection; however, congenital infections mav result in neurologic manifestations in the infant. Exposure to CMV druing pregnancy is possible for nurses in transplantation and neonatal units because many of their patients RF actively excreting the virus. Hnwever, Balfour and Balfour” in a prospective surveillance study found that nurses in renal transplantation and neonatal units are not at an increased occupational risk.
HAZARDS
DURING PREGNANCY
ANESTHETICS Animal studies show anomalies and fetal lethality at high doses of anesthetics. Several studies indicate that female operating room personnel exposed to high levels of anesthetic gases have an increased miscarriage rate. *O Rowland et al” retrospectively examined the effect of nitrous oxide on spontaneous abortion among female dental assistants. They found an association between exposure to high levels of unscavenged nitrous oxide for more than 5 hours a week and reduced fertility in female dental assistants. No decrease in the ability to conceive was found in dental assistants working in offices with scavenged nitrous oxide, regardless of the length of exposure. Scavenging equipment is now standard in hospital operating rooms, thus reducing the levels of exposure by 90% or more and not increasing the rate of spontaneous abortions.
METALS Lead toxicity has been recognized for centuries. In the 1700s, women were removed from the white lead ceramics industry of England because of an increased rate of miscarriage. Lead is one of the most extensively used heavy metals and is a common environmental contaminant. Industries associated with the highest risks of occupatinnel exposure to lead are lead smelting and refining, production and recycling of lead storage batteries. welding and cutting metals coated with lead-based paint, and manlrfactlrring of glass and plastics. Other sources include dust and soil contaminated by automobile exhalist. water from lead pipes, and hnhhics involving ceramics and stain4 glass. Lead easily crosses the placenta and ran cause fetal effects. In 1992, Wnng et al” demonstrated that blood Icvels of lead in pregnant 57
FRATTARELLI
AND MOORE
women are lower than in nonpregnant women. They doubted that this can be attributed solely to the dilutional effect of increased plasma volume. The authors proposed that the decrease in lead levels may be due to increased exertion, deposition in the placenta, or active transfer to the fetus. The Port Pirie cohort study measured IQ scores for 494 7-year-old children from a lead smelting community of Port Pirie, Australia.13 Developmental deficits associated with elevated blood levels had already been reported at ages 2 and 4. The authors of this study found an inverse relationship between IQ at age 7 and both antenatal and postnatal blood lead concentrations. Lead is known to be a reproductive toxicant causing decreased fertility, miscarriages, and stillbirths. For workers in contact with lead, protective equipment and policies must be in place. Respirators, hoods, exhaust ventilation, good personal hygiene, hand and clothes washing, and prohibition of eating, smoking, and drinking in the work area must be enforced. Other heavy metals also cause reproductive effects. Mercury ingestion from contaminated salt or fresh water fish can cause severe CNS damage, as was seen in the Minamata Bay disaster in Japan. Because the fetus is more sensitive to mercury effects than the mother, accidental poisonings can occur without adult symptoms but with significant fetal effects. Cadmium, commonly found in cigarette smoke, has been found to be highly teratogenic in animals at high doses. However, no human studies have documented this theory.
ORGANIC
SOLVENTS
Because of their lipid solubility, many organic solvents cross the placenta readily. Thus, pregnant women and their fetuses are particularly vulnerable to their effects. 58
Organic solvents are used widely in industry and the home. They are found in electronic equipment, dry cleaning fluids, detergents, glues, and paints. Exposure occurs primarily by inhalation or skin absorption. Solvents are highly lipid soluble and thus most commonly will cause skin and CNS toxicity. Several studies have documented adverse pregnancy outcomes with organic solvents. In a large casecontrol study of 1,926 spontaneous abortions, Windham et all4 found that occupational exposure to solvents was associated with an increased rate of spontaneous abortion. The aromatic hydrocarbons (benzene, toluene, and xylene) are the best studied and have been reported to cause facial and limb malformations, growth retardation, and CNS deficiencies. Pearson et alI5 reported on 18 infants with a history of in utero toluene exposure. In addition to other abnormalities, they found that 83% of the infants had craniofacial features similar to fetal alcohol syndrome. For the halogenated hydrocarbons, ketones, and acetone, very little human data exist except for a few case reports. Whereas multiple studies demonstrate that the glycol ethers (ethylene gylcol and its derivatives] cause a decrease in male sperm count, the effect on the pregnant female is less certain.
Conclusion The literature regarding occupational exposure and pregnancy outcome is limited. There are growing experimental and epidemiologic data supportive of an etiologic relationship between workplace exposures and some adverse reproductive outcomes. Existing data, however, tend to come from relatively small studies. Most research has focused on mutagens. Studies of occupational exposure to women
have mainly addressed miscarriage. Only a few chemicals can definitely be incriminated as being toxic reproductive agents in humans. A large number of chemicals have been found to be detrimental to animals, without being tested in humans. However, most chemicals have never been studied. When evaluating a patient for potential hazardous exposure, the physician must remember to counsel the patient regarding background reproductive outcomes. The patient must be aware that lo-15% of the general population is infertile, lo-20% of all recognized pregnancies end in miscarriage, and Z-3% of all babies born have major birth defects. It must be stressed that a healthy pregnancy outcome can never be guaranteed. Many factors may influence successful pregnancy outcomes in a multifactorial way. It is well known that stress, work hours, and work intensity can all play a role in ovulation and pregnancy outcomes. A thorough assessment of the potential impact of environmental and occupational factors, including chemicals, viruses, radiation, noise, temperature, stress, physical exertion, and working position, must be made before informing the patient of the potential workplace hazards. Evaluation and management of the pregnant patient begins with an assessment of potential hazards, health effects, and reproductive risks. A physical examination looking for evidence of toxic exposure, especially skin changes, is an initial method to assessexposure. A starting point for identification of chemicals used on the job is to review material safety data sheets, which identify the composition, properties, and health effects of chemicals used. However, these forms frequently contain inadequate information regarding reproductive health effects, and thus further investigation is needed. The employer can also be asked to furnish indusPrim
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Update
ObKyns
trial hygiene data regarding exposure measurements. While protective for the adult employee, existing regulatory safeguards such as permissible exposure limits are not designed to ensure fetal safety when the mother is working. Therefore, the employer may be in legal compliance with all safety requirements and yet reproductive hazards may exist. Obtaining the assistance of occupational health consultants with expertise in reproductive hazards will facilitate the investigation for potential hazards. If these consultants are not available, there are several computer databases, such as the Teratogen Information System (TERIS), Toxnet, Reprotox, and Reprorisk, that may be helpful in identifying workplace risks. Additionally, there are risk hotlines available that can provide valuable information. The Organization of Teratogen Information Services (617-787-4957) will provide telephone numbers of pregnancy hotlines available in the United States and Canada. References 1. Homer
CJ,
Work-related
Volume
5, Number
James
SA,
psychosocial
1, 1998
Siegel
E.
stress
natal units.
and risk of preterm, low birthweight delivery. Am J Public Health 1990; 80:173-7. 2.
pregnancy on the risk of severe
16.
Baird DD, Wilcox AJ, Weinberg CR. Using time to pregnancy to study environmental exposures. Am J Epidemiol 1986;124:470-80. TM, Grajewski BA, Hor5. Schnorr nung RW, et al. Video display terminals and the risk of spontaneous abortion. N Engl J Med 1991;324: 4.
11.
12.
13.
727-33.
Lalande NM, Hetu R, Lambert J. Is occupational noise exposure during pregnancy a risk factor of damage to the auditory system of the fetus? Am J Indust Med 1986;10:427-35. 7. Shiota K. Neural tube defects and maternal hyperthermia in early pregnancy: epidemiology in a hu6.
14.
15.
man embryo population. Am J Med Genet 1982;12:281-8. Milunsky A, Ulcickas M, Rothman KJ, et al. Maternal heat exposure and neural tube defects. JAMA 1992;268:882-5. 9. Balfour C, Balfour H. Cytomegalovirus is not an occupational risk for nurses in renal transplant and neo-
1986;256:1909-
10. Guirguis
Spinillo A, Capuzzo E, Colonna L, et al. The effect of work activity in
preeclampsia. Aust N Z J Obstet Gynaecol 1995;35:380. 3. Ogilvy-Stuart L, Shalet S. Effect of radiation on the human reproductive system. Environ Health Perspect Suppl1993;lOl Suppl2:109-
JAMA
14.
SS, Pelmear PL, Roy ML, et al. Health effects associated with exposure to anesthetic gases in Ontario hospital personnel. Br J Ind Med 1990;47:490-7. Rowland AS, Baird DD, Weinberg CR, et al. Reduced fertility among women employed as dental assistants exposed to high levels of nitrous oxide. N Engl J Med 1992:327: 993-7. Wong GP, Ng TL, Martin TR, et al. Effects of low-level lead exposure in utero. Obstet Gynecol Surv 1992;47: 285-9. Baghurst PA, McMichael AJ, Wigg NR, et al. Environmental exposure to lead and children’s intelligence at the age of seven years: the Port Pirie cohort study. N Engl J Med 1992;327:1279-84. Windham GC, Shusterman D, Swan SH, et al. Exposure to organic solvents and adverse pregnancy outcome. Am J Indust Med 1991;20: 241-59. Pearson MA, Hoyme HE, Seaver LH, et al. Toluene embryopathy: delineation of the phenotype and comparison with fetal alcohol syndrome. Pediatrics 1994;93:211-5.
8.
Address correspondenceand reprint requeststo John L. Frattarelli, MD, Walter Reed Army Medical Center, 6900 Georgia Avenue, Washington, DC 203075001.
59
WORKPLACE HAZARDS DURING PREGNANCY John L. Frattarelli, MD, CPT, MC,* USA, and Gregory R. Moore, CDR, MC,t USN
Currently, very little is known about potential reproductive hazards found in the workplace. Yet, every day pregnant women are exposed to toxins and physical agents that are potentially harmful to them and theirfetuses. Concerned obstetric patients frequently inquire about the possibility that agents they encounter on their jobs may have an adverse impact on their pregnancy. A variety of workplace exposures have been studied, and existing data allow us to make appropriate recommendations to working women. Unfortunately, data are limited regarding the majority of exposures. Certainly, the reproductive risks of radiation and heavy metals have been known for years. This is not the case with most other exposures. With the female workforce growing, more women are being exposed to these potential reproductive hazards. In this article, we review the recent literature to assess the hazards to the pregnant female and the fetus from workplace exposure to physical stress, radiation, lead, biologic agents, anesthetics, and solvents. In addition, we offer guidelines and resources for evaluating and managing the hazards found in the workplace. (P rim Care Update OblGyns 1998;5:54-59. 0 1998
Elsevier reserved.)
Science
Inc.
All
rights
From the Department of Obstetrics and Gynecology. *Walter Reed Army Medical Center, Washington, DC; and tNationa1 Naval Medical Center, Bethesda, Maryland. The views expressed herein are those of the authors and do not reflect the official policy or position of the Department of the Army, the Department of the Navy. the Department of Defense, or the U.S. Government.
Studying workplace reproductive hazards is a relatively new field for research and clinical medicine. Approximately two thirds of women of childbearing age have jobs outside the home. More than 1 million of these women become pregnant each year. As more women work outside of the home, they are exposed to a variety of occupational risks, including possible reproductive hazards. There is a general lack of valid data demonstrating the toxicity of potential occupational hazards in pregnancy. There is an even greater paucity of valid information and research about the adverse effects of preconceptional exposures. What is known is that there are a variety of adverse reproductive endpoints and environmental exposures, on and off the job, that may play a role in reproductive outcomes. Ten percent to 20% of all recognized pregnancies end in miscarriage between the fourth and 20th week. Additionally, 2-3% of all newborns have major congenital anomalies. Approximately 60% of these anomalies have no known cause. Some likely involve environmental or occupational factors. The pregnant woman is justifiably concerned about the potential dangers in the workplace that may affect her pregnancy. As manufacturing processes change, new technology comes on line, and women work in traditionally male fields, new reproductive hazards will emerge and known hazards may become more important. Approxi-
54
Inc.,
0 1998
Elsevier
Science
all rights
reserved.
1068-607X/98/$19.00
mately 60,000 chemicals are in common use, with an additional 600 new chemicals entering the marketplace each year. Few of these chemicals have been tested for developmental toxicity in experimental animals, and even fewer in human subjects. Our knowledge about the potential reproductive risk from even low-level exposure to a mixture of agents, which is common in the workplace, is even less certain. Toxic exposure can cause a range of effects, including germ cell alteration, menstrual irregularity, embryologic effects, and implantation abnormalities. Ovarian toxicity has been linked to ionizing radiation, chemotherapy, tobacco use, and other exposures. Although better protected by virtue of the bloodtestes barrier, the male gonads can also be harmed. Damage to sperm production, however, is often reversible because the male, unlike the female, has a renewing germ cell pool. During pregnancy, the timing of the insult is crucial to the embryologic effect. In the early preimplantation period a teratogenic insult probably creates an “all or none” effect. When the embryo consists of only a few cells, loss of one or two of these cells will result in either the death of the embryo or the remaining toti-potential cells will take over the functions of the lost cells, resulting in an intact organism. Damage during the embryologic period, which extends from implantation to day 56 of gestation, may also cause death or gross structural abnormalities. During the fetal period, day 56 of gestation until birth, dangerous exposures are most likely to produce growth and central nervous
. PI1 SlO68.607X(97)00114-5
Prim
Care
Update
ObiGyns
WORKPLACE
system (CNS) deficits, although serious teratogenic effects can occur after exposure to agents like radiation and viruses during the third trimester.
Ergonomics Many studies have shown that working women have better pregnancy outcomes than unemployed women. However, frequently confounding factors such as age, education, family size, and access to medical care are present. Working women tend to have better health insurance and other socioeconomic factors that may result in better compliance with prenatal care and counteract small occupational risks. Recent reports suggest an association with strenuous physical work, preterm delivery, and low birth weight. In a large study conducted in New York, Homer et all examined the combined outcome of preterm delivery and low birth weight in young disadvantaged white, black, and Hispanic women. After adjusting for confounding variables, they found an increased risk of low birth weight and preterm delivery in women who reported high levels of occupational physical exertion. Many physiologic changes occur during pregnancy that can affect the type and duration of work that women can safely and comfortably perform. Early in her pregnancy, a woman may experience nausea, vomiting, and dizziness. Jobs where odors or motion are present may exacerbate these normal and expected symptoms. Physiologic changes in the cardiovascular system during pregnancy produce an increase in blood volume, cardiac output, heart rate, inferior vena caval pressure, and a decrease in diastolic blood pressure. These cardiovascular alterations can be affected by temperature, humidity, and barometric pressure. Pulmonary Volume
5. Number
1. 1998
changes during pregnancy create an increased tidal volume, minute ventilation, oxygen demand, work of breathing, capillary dilation throughout the respiratory tract, and decreased residual lung volume. Smoke, asphyxiant agents, and irritant gasescan affect the pulmonary changes experienced during pregnancy. The additional work of breathing during pregnancy may make the use of personnel protective devices, such as respirators, dilficult. Likewise, the increased metabolic demands of pregnancy can hinder the woman’s ability to perform strenuous, repetitive tasks. Musculoskeletal changes cause an increase in lordosis of the lumbosacral spine and a posterior shift of the patient’s center of gravity. These changes place the pregnant worker at an increased risk for loss of balance, lower back ache, and muscle strains. She should be warned to avoid wearing high heels and lifting heavy items. The enlarging uterus makes it necessary to lift loads further from the axial skeleton, thus markedly increasing the work of lifting. The pregnant patient is also at an increased risk for repetitive motion injuries when performing tasks such as typing and playing musical instruments. An increase in maternal metabolic rate coupled with the fetal demand for heat dissipation makes the pregnant woman less tolerant to hot, humid environments and working conditions. Jobs requiring protective clothing can add to this heat burden. Furthermore, standing for long periods can decrease uteroplacental blood flow and may lead to a decrease in birth weight. In general, workloads handled easily before pregnancy are usually well tolerated during pregnancy. Simple modifications such as decreasing the work pace, foot rests to relieve lumbosacral disc pressure while sitting, and increased rest breaks are often sufficient enough to
HAZARDS
DURING
PREGNANCY
allow the woman to continue working safely. Fortunately, some physiologic adaptations may help protect the fetus from environmental exposures. The increase in blood volume may dilute the concentration of toxins reaching the maternal tissues. Likewise, increases in renal plasma flow and glomerular filtration rate allow for an increased rate of elimination of toxic metabolites. In a recent case-control study, Spinillo et al2 evaluated 160 nulliparous patients with severe preeclampsia and 320 normotensive nulliparous control subjects. They divided the patients into four groups based on their level of activity. They concluded that there was a significant linear trend relating degree of physical activity at work to the risk of preeclampsia. However, for every study supporting physical work during pregnancy as a hazard, there is also an article advocating that work and pregnancy outcome are unrelated. IONIZING RAIMATI~N Ionizing radiation is so called because it has sufficient energy to displace orbital electrons, resulting in the formation of electronically charged ions in matter. It includes x-rays, y rays, (Y particles, p particles, and neutrons. The principal unit of exposure is the roentgen, defined as the measure of the amount of ionizations produced in the air. Units of absorbed radiation include the Gray and the rad. One Gray equals 100 rad or 100 rem. Different types of radiation produce differing amounts of biologic damage. The sievert (sv) or rem (1 sv = 100 rem) adjusts for the difference in effect produced by the different types of radiation. X-rays, y rays, and /3 particles all produce equivalent damage; however, cy particles produce 20 times the damage of the others. Fortunately, (Yparticles penetrate poorly, but they are hazardous if consumed in food or water. 55
Everyone is continuously exposed to low-dose background radiation found in cosmic rays, soil, rock, air, and natural radioisotopes. Background radiation exposure increases at high altitudes because the atmosphere filters out fewer cosmic rays. This information can be pertinent to people whose occupations require frequent flying. An individual flying from New York to Tokyo at the usual altitude of 40,000 feet will receive radiation that is equivalent to approximately two chest x-rays. Workplace radiation exposures usually result from whole-body external radiation. The most significant exposures occur during accidents on the job when the radiation source is no longer contained by protective measures. Occupational sources include nuclear fuel, diagnostic x-ray, radioisotopes, and radioactive minerals. The degree of damage produced by ionizing radiation is influenced by several factors, including type, dose, dose disand target tissue tribution, sensitivity. Rapidly dividing cells of the embryo and reproductive germinal epithelium are particularly radiosensitive. The complex development of the CNS, which takes place throughout pregnancy and into postpartum life, makes it a common target for radiation damage. The gonads are highly sensitive to the effects of irradiation, with resulting temporary and permanent effects on fertility depending on the dose of radiation received.3 Permanent sterility has been reported in women and men from a single dose of 600 rads and 400 rads, respectively. Effects of prenatal exposure are highly time dependent, ranging from an all or none effect during preimplantation to teratogenic effects, especially microcephaly and eye anomalies during organogenesis. Mental retardation, growth restriction, and CNS deficits can occur with exposure later in gestation. 56
However, there seems to be a radiation threshold, in that there have been no observable fetal effects with an exposure of less than 5 rads. With the exception of a lumbosacral spine series (0.64 rem), bone scan (0.5 rem), and intravenous pyelogram (0.64 rem), there are very few diagnostic radiation studies that result in doses of more than 0.5 rem. Occupational Safety and Health Administration occupational limits for ionizing radiation to the adult gonads are 1.25 rems per calendar quarter or 5 rems per year. The National Council on Radiation Protection and Measurements suggests that occupational exposure to an embryo or fetus not exceed 0.5 rems total dose.4 Although radiation exposure is a definite threat to the pregnant patient given the proper precautions, most patients working with ionizing radiation can continue employment. When counseling patients regarding the risk of radiation exposure, the dose, frequency, and precise timing of the exposure should be estimated. Radiation safety personnel can obtain radiation badge readings and assist in determining the amount of exposure.
NONIONIZING
RADIATION
Nonionizing radiation is ubiquitous. Radiofrequency radiation comes from television, radio, radar, microwaves, computer terminals, heating blankets, toasters, and more. Nonionizing radiation damages tissues not by ionization but by cellular heating. The eye, testes, CNS, and developing embryo potentially have high sensitivities to the thermal effects of radiofrequency radiation. However, industrial and home exposure are well below the threshold to cause teratogenic effects owing to modern protective devices, such as screens in microwave ovens that are 100% effective in shielding all radiation.
Video display terminals (VDTs), which produce very low frequency and extremely low frequency radiation, are common both at work and in the home. Physicians frequently encounter questions from patients concerning the safety of these devices. The cathode ray tubes of VDTs are similar to television tubes and emit x-rays. However, this ionizing radiation is well absorbed by the glass screen and ionizing radiation emissions are negligible. Literature from the early 1980s contained several cases concerning the potential reproductive effects and increased miscarriage rates in females exposed to VDTs during pregnancy. However, most subsequent epidemiologic analyses found equivocal or no effect on pregnancies associated with VDT use. The most complete study of VDTs and pregnancy was reported in 1991 by researchers at the National Institution for Occupational Safety and Health.5 Schnorr et al used a cohort investigation involving directory assistance operators who used only VDTs and general telephone operators who used work stations without VDTs. They concluded that the use of VDTs and exposure to the accompanying electromagnetic fields were not associated with an increase in spontaneous abortions. Thus, there is no scientific evidence to suggest that women need to curtail or discontinue the use of VDTs during pregnancy. Noise is transmitted clearly through the abdomen; some frequencies are actually accentuated. There is no effective way to shield the fetus from noise. There is some evidence that in utero exposure to loud noises greater than 85 dBA can cause hearing loss. Lalande et al” evaluated 131 children whose mothers had worked at least 1 month during pregnancy in a setting where noise levels ranged from 65 to 95 dBA. A strong dose-response relationship was noted between noise level during pregnancy and Prim
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WORKPLACE subsequent hearing loss in children. Among children whose mothers were exposed to levels of 85-95 dBA during the course of their pregnancy, 24% had significant hearing loss; however, only 12.9% experienced hearing loss when exposed to noise levels less than 85 dBA. Exposure to heat and hot environments can occur in a variety of industries and occupations. In extreme situations, the precise regulation of internal body temperature can be overcome by environmental heat. Several studies have linked an increase in the core temperature during early pregnancy to neural tube defects. Shiota,7 in a study involving human abortus specimens, found a highly significant association between reported febrile illness of 39 C during pregnancy and exencephaly. Because the most common cause of an increased core temperature in the pregnant female is maternal fever, studies have tended to rely on this association. As with most studies of pregnancy outcomes, however, recall bias is a common problem. It is conceivable that in certain working conditions, such as hot, humid climates and industrial operation (mining and metal processing, laundering, construction, food preparation, textiles, canning, and manufacturing of plastics, rubber, glass, and chemicals), the maternal core temperature could rise to the critical level of 39 C. Milunsky et al8 in 1992 reported on a cohort of 23,491 women in a prospective follow-up study. They found that first-trimester maternal heat exposure in the form of hot tubs, sauna, or fever was associated with an increased risk of neural tube defects. Exposure to electric blankets was not associated with an increased risk. Therefore, women who have experienced hyperthermic episodes during early pregnancy should be counseled about the possibility of teratogenic effects Volume
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and offered a-fetoprotein screening and level 2 ultrasound evaluation. BIOLOGIC
AGENTS
Workers in the health care system, schools, and day care centers may be exposed to a number of potentially harmful infectious agents, including rubella, parvovirus, cytomegalovirus (CMV), varicella, hepatitis B, and human immunodeficiency virus. All workers in such areas should strictly adhere to universal precautions and infection control measures. In doing this, they will greatly decrease their risk of infection. Rubella, CMV, and varicella are teratogenic after maternal exposures well into the second trimester. Specific immunoglobulins can be used prophylactically in some circumstances after contact with infected patients and children. Although vaccines are available for rubella, varicella, hepatitis B, mumps, and measles, there are still a significant number of nonimmune individuals in the population, especially in immigrant communities. However, the live vaccines for measles, mumps, rubella, polio, and yellow fever are contraindicated in pregnancy because of the throrctical risk of transmission of the virus to the fetus. Not only is CMV ubiquitous, but it remains infectious on surfaces, and approximately half of the adult population is susceptible. The virus infects the fetus vertically. Most mothers and fetuses are asymptomatic during CMV infection; however, congenital infections mav result in neurologic manifestations in the infant. Exposure to CMV druing pregnancy is possible for nurses in transplantation and neonatal units because many of their patients RF actively excreting the virus. Hnwever, Balfour and Balfour” in a prospective surveillance study found that nurses in renal transplantation and neonatal units are not at an increased occupational risk.
HAZARDS
DURING PREGNANCY
ANESTHETICS Animal studies show anomalies and fetal lethality at high doses of anesthetics. Several studies indicate that female operating room personnel exposed to high levels of anesthetic gases have an increased miscarriage rate. *O Rowland et al” retrospectively examined the effect of nitrous oxide on spontaneous abortion among female dental assistants. They found an association between exposure to high levels of unscavenged nitrous oxide for more than 5 hours a week and reduced fertility in female dental assistants. No decrease in the ability to conceive was found in dental assistants working in offices with scavenged nitrous oxide, regardless of the length of exposure. Scavenging equipment is now standard in hospital operating rooms, thus reducing the levels of exposure by 90% or more and not increasing the rate of spontaneous abortions.
METALS Lead toxicity has been recognized for centuries. In the 1700s, women were removed from the white lead ceramics industry of England because of an increased rate of miscarriage. Lead is one of the most extensively used heavy metals and is a common environmental contaminant. Industries associated with the highest risks of occupatinnel exposure to lead are lead smelting and refining, production and recycling of lead storage batteries. welding and cutting metals coated with lead-based paint, and manlrfactlrring of glass and plastics. Other sources include dust and soil contaminated by automobile exhalist. water from lead pipes, and hnhhics involving ceramics and stain4 glass. Lead easily crosses the placenta and ran cause fetal effects. In 1992, Wnng et al” demonstrated that blood Icvels of lead in pregnant 57
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women are lower than in nonpregnant women. They doubted that this can be attributed solely to the dilutional effect of increased plasma volume. The authors proposed that the decrease in lead levels may be due to increased exertion, deposition in the placenta, or active transfer to the fetus. The Port Pirie cohort study measured IQ scores for 494 7-year-old children from a lead smelting community of Port Pirie, Australia.13 Developmental deficits associated with elevated blood levels had already been reported at ages 2 and 4. The authors of this study found an inverse relationship between IQ at age 7 and both antenatal and postnatal blood lead concentrations. Lead is known to be a reproductive toxicant causing decreased fertility, miscarriages, and stillbirths. For workers in contact with lead, protective equipment and policies must be in place. Respirators, hoods, exhaust ventilation, good personal hygiene, hand and clothes washing, and prohibition of eating, smoking, and drinking in the work area must be enforced. Other heavy metals also cause reproductive effects. Mercury ingestion from contaminated salt or fresh water fish can cause severe CNS damage, as was seen in the Minamata Bay disaster in Japan. Because the fetus is more sensitive to mercury effects than the mother, accidental poisonings can occur without adult symptoms but with significant fetal effects. Cadmium, commonly found in cigarette smoke, has been found to be highly teratogenic in animals at high doses. However, no human studies have documented this theory.
ORGANIC
SOLVENTS
Because of their lipid solubility, many organic solvents cross the placenta readily. Thus, pregnant women and their fetuses are particularly vulnerable to their effects. 58
Organic solvents are used widely in industry and the home. They are found in electronic equipment, dry cleaning fluids, detergents, glues, and paints. Exposure occurs primarily by inhalation or skin absorption. Solvents are highly lipid soluble and thus most commonly will cause skin and CNS toxicity. Several studies have documented adverse pregnancy outcomes with organic solvents. In a large casecontrol study of 1,926 spontaneous abortions, Windham et all4 found that occupational exposure to solvents was associated with an increased rate of spontaneous abortion. The aromatic hydrocarbons (benzene, toluene, and xylene) are the best studied and have been reported to cause facial and limb malformations, growth retardation, and CNS deficiencies. Pearson et alI5 reported on 18 infants with a history of in utero toluene exposure. In addition to other abnormalities, they found that 83% of the infants had craniofacial features similar to fetal alcohol syndrome. For the halogenated hydrocarbons, ketones, and acetone, very little human data exist except for a few case reports. Whereas multiple studies demonstrate that the glycol ethers (ethylene gylcol and its derivatives] cause a decrease in male sperm count, the effect on the pregnant female is less certain.
Conclusion The literature regarding occupational exposure and pregnancy outcome is limited. There are growing experimental and epidemiologic data supportive of an etiologic relationship between workplace exposures and some adverse reproductive outcomes. Existing data, however, tend to come from relatively small studies. Most research has focused on mutagens. Studies of occupational exposure to women
have mainly addressed miscarriage. Only a few chemicals can definitely be incriminated as being toxic reproductive agents in humans. A large number of chemicals have been found to be detrimental to animals, without being tested in humans. However, most chemicals have never been studied. When evaluating a patient for potential hazardous exposure, the physician must remember to counsel the patient regarding background reproductive outcomes. The patient must be aware that lo-15% of the general population is infertile, lo-20% of all recognized pregnancies end in miscarriage, and Z-3% of all babies born have major birth defects. It must be stressed that a healthy pregnancy outcome can never be guaranteed. Many factors may influence successful pregnancy outcomes in a multifactorial way. It is well known that stress, work hours, and work intensity can all play a role in ovulation and pregnancy outcomes. A thorough assessment of the potential impact of environmental and occupational factors, including chemicals, viruses, radiation, noise, temperature, stress, physical exertion, and working position, must be made before informing the patient of the potential workplace hazards. Evaluation and management of the pregnant patient begins with an assessment of potential hazards, health effects, and reproductive risks. A physical examination looking for evidence of toxic exposure, especially skin changes, is an initial method to assessexposure. A starting point for identification of chemicals used on the job is to review material safety data sheets, which identify the composition, properties, and health effects of chemicals used. However, these forms frequently contain inadequate information regarding reproductive health effects, and thus further investigation is needed. The employer can also be asked to furnish indusPrim
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trial hygiene data regarding exposure measurements. While protective for the adult employee, existing regulatory safeguards such as permissible exposure limits are not designed to ensure fetal safety when the mother is working. Therefore, the employer may be in legal compliance with all safety requirements and yet reproductive hazards may exist. Obtaining the assistance of occupational health consultants with expertise in reproductive hazards will facilitate the investigation for potential hazards. If these consultants are not available, there are several computer databases, such as the Teratogen Information System (TERIS), Toxnet, Reprotox, and Reprorisk, that may be helpful in identifying workplace risks. Additionally, there are risk hotlines available that can provide valuable information. The Organization of Teratogen Information Services (617-787-4957) will provide telephone numbers of pregnancy hotlines available in the United States and Canada. References 1. Homer
CJ,
Work-related
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Siegel
E.
stress
natal units.
and risk of preterm, low birthweight delivery. Am J Public Health 1990; 80:173-7. 2.
pregnancy on the risk of severe
16.
Baird DD, Wilcox AJ, Weinberg CR. Using time to pregnancy to study environmental exposures. Am J Epidemiol 1986;124:470-80. TM, Grajewski BA, Hor5. Schnorr nung RW, et al. Video display terminals and the risk of spontaneous abortion. N Engl J Med 1991;324: 4.
11.
12.
13.
727-33.
Lalande NM, Hetu R, Lambert J. Is occupational noise exposure during pregnancy a risk factor of damage to the auditory system of the fetus? Am J Indust Med 1986;10:427-35. 7. Shiota K. Neural tube defects and maternal hyperthermia in early pregnancy: epidemiology in a hu6.
14.
15.
man embryo population. Am J Med Genet 1982;12:281-8. Milunsky A, Ulcickas M, Rothman KJ, et al. Maternal heat exposure and neural tube defects. JAMA 1992;268:882-5. 9. Balfour C, Balfour H. Cytomegalovirus is not an occupational risk for nurses in renal transplant and neo-
1986;256:1909-
10. Guirguis
Spinillo A, Capuzzo E, Colonna L, et al. The effect of work activity in
preeclampsia. Aust N Z J Obstet Gynaecol 1995;35:380. 3. Ogilvy-Stuart L, Shalet S. Effect of radiation on the human reproductive system. Environ Health Perspect Suppl1993;lOl Suppl2:109-
JAMA
14.
SS, Pelmear PL, Roy ML, et al. Health effects associated with exposure to anesthetic gases in Ontario hospital personnel. Br J Ind Med 1990;47:490-7. Rowland AS, Baird DD, Weinberg CR, et al. Reduced fertility among women employed as dental assistants exposed to high levels of nitrous oxide. N Engl J Med 1992:327: 993-7. Wong GP, Ng TL, Martin TR, et al. Effects of low-level lead exposure in utero. Obstet Gynecol Surv 1992;47: 285-9. Baghurst PA, McMichael AJ, Wigg NR, et al. Environmental exposure to lead and children’s intelligence at the age of seven years: the Port Pirie cohort study. N Engl J Med 1992;327:1279-84. Windham GC, Shusterman D, Swan SH, et al. Exposure to organic solvents and adverse pregnancy outcome. Am J Indust Med 1991;20: 241-59. Pearson MA, Hoyme HE, Seaver LH, et al. Toluene embryopathy: delineation of the phenotype and comparison with fetal alcohol syndrome. Pediatrics 1994;93:211-5.
8.
Address correspondenceand reprint requeststo John L. Frattarelli, MD, Walter Reed Army Medical Center, 6900 Georgia Avenue, Washington, DC 203075001.
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